The objectives of this research are to understand the chemical and enzymatic mechanisms by which pyrimidine rings are alkylated and halopyrimidines are dehalogenated. These reactions are of importance in the understanding and prevention of cancer, since (a) high RNA methylase activity is a predominant feature of malignant tissue, (b) anti-tumor and anti-leukemic drugs, such as 5-FdUMP and the folic acid antagonists, have as their targets enzymes involved in the "thymidylate cycle", (c) 5-halopyrimidine nucleosides are important anti-viral agents which in vivo are degraded to pyrimidine bases and then dehalogenated, (d) the halopyrimidine nucleoside anti-viral agents are potent activators of certain leukemia and other viruses. Considering the reactivity of halopyrimidine and halodihydropyrimidines with naturally occurring nucleophilic reagents, a better understanding of these reactions might elucidate the reasons for virus activation by these compounds, and (e) it should also be noted that certain chemical reactions which proceed by mechanisms analogous to enzymatic pyrimidine alkylation can convert uracil to dihydrouracil and cytosne to uracil. Reagents, such as bisulfite, rapidly promote these reactions and have been shown to be mutagenic. Since bisulfite is used in both the food and paper industries, and is generated by the hydration of SO2, a common air pollutant, an understanding of how this compound reacts with pyrimidine bases can have considerable environmental impact. BIBLIOGRAPHIC REFERENCES: F.A. Sedor and E.G. Sander. The Dehalogenation of 5-Bromo-6-methoxy-5, 6-dihydrothymine by cysteine. J. Am. Chem. Soc. 98, 2413, 1976. F.A. Sedor and E.G. Sander. Inhibition of uricase by substituted pyrimidines. Biochem. Biophys. Res. Comm. 75, 406, 1977.